title: Gpr125 modulates Dishevelled distribution and planar cell polarity signaling.
abstract: During vertebrate gastrulation, Wnt/planar cell polarity (PCP) signaling orchestrates polarized cell behaviors underlying convergence and extension (C&E) movements to narrow embryonic tissues mediolaterally and lengthen them anteroposteriorly. Here, we have identified Gpr125, an adhesion G protein-coupled receptor, as a novel modulator of the Wnt/PCP signaling system. Excess Gpr125 impaired C&E movements and the underlying cell and molecular polarities. Reduced Gpr125 function exacerbated the C&E and facial branchiomotor neuron (FBMN) migration defects of embryos with reduced Wnt/PCP signaling. At the molecular level, Gpr125 recruited Dishevelled to the cell membrane, a prerequisite for Wnt/PCP activation. Moreover, Gpr125 and Dvl mutually clustered one another to form discrete membrane subdomains, and the Gpr125 intracellular domain directly interacted with Dvl in pull-down assays. Intriguingly, Dvl and Gpr125 were able to recruit a subset of PCP components into membrane subdomains, suggesting that Gpr125 may modulate the composition of Wnt/PCP membrane complexes. Our study reveals a role for Gpr125 in PCP-mediated processes and provides mechanistic insight into Wnt/PCP signaling.
authors.affiliation: Neuroscience Graduate Program, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Isabelle
authors.initials: I
authors.lastname: Roszko
authors.forename: Diane S
authors.initials: DS
authors.lastname: Sepich
authors.forename: Mingwei
authors.initials: M
authors.lastname: Ni
authors.forename: Heidi E
authors.initials: HE
authors.lastname: Hamm
authors.forename: Florence L
authors.initials: FL
authors.lastname: Marlow
authors.forename: Lilianna
authors.initials: L
authors.lastname: Solnica-Krezel
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D002465:Cell Movement; D016764:Cell Polarity; D000072261:Dishevelled Proteins; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D009154:Mutation; D010750:Phosphoproteins / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D014921:Wings, Animal / Q000166:cytology / Q000196:embryology; D060449:Wnt Signaling Pathway; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; D010750:Phosphoproteins; D043562:Receptors, G-Protein-Coupled; D029961:Zebrafish Proteins; C583225:adgra3 protein, zebrafish
keywords: Convergence and extension; Facial branchiomotor neuron; Gastrulation movements; Zebrafish